crossing96/oncoscreening huggingface dataset:
"Urothelial carcinoma in situ with ""early papillary formation"" vs ""lateral spread/shoulder lesion"" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations."	"OBJECTIVES: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC. METHODS: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists. RESULTS: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as ""CIS with early papillary features"" (38% for groups 1 and 2 vs 13% for group 3). Among all 3 groups, group 1 was most likely to diagnose concomitant CIS and PUC in the same specimen but in different tissue fragments (58%). Pagetoid spread was reported to favor CIS predominantly by group 1 (61%). Urologists felt that the term lateral spread/shoulder was unclear (75%) and preferred early PUC (44%) or PUC with early growth (44%). Half (53%) of urologists felt that reporting CIS instead of lateral spread of PUC would change management. CONCLUSIONS: Documentation of flat lesions lacks consensus among pathologists and may benefit from standardized terminology. Moreover, the distinction between CIS and early or lateral spread of PUC is not always clear to urologists and can influence disease management."	bladder
A French Multicenter Real-Life Study on the Biological and Clinical Parameters Associated With Response to Immune Checkpoint Inhibitors (ICIs) in Second-Line Treatment of Advanced Urothelial Carcinoma: Impact of Antibiotics Administration at the Time of ICIs Initiation.	BACKGROUND: After failure of first-line chemotherapy, standard of care for advanced urothelial cancer (aUC) is immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway. Several prognostic models (Bajorin and Bellmunt scores) have been evaluated, but only in the context of chemotherapy. OBJECTIVE: To study whether the variables in these scores and new emerging clinical and biological criteria have an impact on the probability of objective response in aUC treated with ICIs in 2nd-line setting and beyond. MATERIALS AND METHODS: Between October 2016 and March 2023, we included 168 patients treated with ICIs in 2nd-line setting or more in 2 French centers. Variables of interest were selected after a literature review and collected retrospectively. Analyses used log-rank test and multivariate models (binary logistic and Cox regressions). RESULTS AND LIMITATIONS: Median age at diagnosis was 68 years. Patients presented with bladder tumors in 73.8% and upper urinary tract tumors in 26.2%. 63.7% of patients had received only one line of chemotherapy before ICIs. Median follow-up after starting ICIs was 8.9 months. The variables statistically associated with objective response were: - The presence of locally advanced or lymph node-only disease compared with visceral involvement (adjusted Odds Ratio 0.19, 95% confidence interval [0.06-0.55], P = .002) and bone-only involvement (aOR 0.22 [0.08-0.64], P = .005) - The absence of antibiotic therapy the month before/after ICIs initiation (aOR 0.31 [0.12-0.84], P = .021). Limitations included retrospective design and small number of patients included. CONCLUSION: This real-life study from 2 French centers found a higher likelihood of objective response: - In the absence of antibiotic therapy at ICIs initiation: - In locally advanced or lymph node-only disease, in contrast to visceral or bone-only disease. Our results suggest that negative impact of antibiotic therapy on the response to ICIs needs to be further investigated to optimize the management of these patients.	bladder
Statin use after cancer diagnosis and survival among patients with cancer.	PURPOSE: The association between statin use and cancer survival has been investigated in previous studies with conflicting findings. This study aimed to assess the association between statin use following cancer diagnosis and survival in six common cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Individuals aged ≥ 66 years diagnosed with prostate cancer, colorectal cancer, lung cancer, bladder cancer, pancreatic cancer, or non-Hodgkin lymphoma (NHL) from 2008 through 2017 were identified. Statin use was defined as two or more statin prescription fills after cancer diagnosis. Time-dependent Cox proportional hazard regression models were used to estimate the association between statin use and cancer-specific mortality for each cancer. RESULTS: This study included 34,618 patients with prostate cancer (median follow-up 4.0 years), 20,579 with colorectal cancer (2.9 years), 20,133 with lung cancer (1.7 years), 6,163 with bladder cancer (2.1 years), 4,538 with pancreatic cancer (0.8 years), and 3,270 with NHL (2.9 years). Statin use post-diagnosis was associated with a reduced risk of cancer-specific mortality in lung cancer (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.74-0.88) and pancreatic cancer (HR, 0.72; 95% CI, 0.59-0.87). The association was not statistically significant for prostate cancer, colorectal cancer, bladder cancer, or NHL. A dose-response relationship by duration of statin use was observed in lung cancer and pancreatic cancer. CONCLUSION: Statin use after cancer diagnosis appears associated with improved survival in lung cancer and pancreatic cancer. Clinical trials of statin therapy in lung and pancreatic cancer patients are warranted to confirm these findings.	bladder
Patient-specific adaptive planning margin for whole bladder radiation therapy.	BACKGROUND: Whole bladder irradiation is an organ preservation treatment approach for muscle-invasive bladder cancer (MIBC). Conventional planning margins, typically 15-20 mm, increase normal tissue toxicity and limit possible dose escalation. PURPOSE: The study aimed to develop a patient-specific adaptive margin recipe for whole bladder irradiation to minimize the planning target volume (PTV) while preserving adequate dose coverage. METHODS: Sixteen patients who received whole-bladder irradiation were retrospectively selected for this study. We proposed a patient-specific anisotropic adaptive margin recipe, derived from the first five fractions of kV-CBCTs, to account for inter-fractional bladder changes. This recipe was validated using kV-CBCTs from fractions six to ten and the final five fractions. The goal was to achieve a residual volume, defined as the percentage of daily bladder volume (V(daily)) outside the PTV, of less than 5%. Adaptive and conventional plans were created using proposed and conventional margins, respectively. A dosimetric comparison of targets and organs-at-risk (OARs) was performed between the two approaches. RESULTS: (V(daily)) decreased throughout the treatment course. The most notable inter-fractional bladder variations were in the superior and anterior directions. The patient-specific anisotropic adaptive margins, averaging 6 mm (± 2.9 mm), achieved a residual volume of less than 5%. Compared to conventional planning, the adaptive approach reduced PTV volume by an average of 135.3 cc (± 46.6 cc). A significant correlation (p < 0.05) was identified between residual volume and adaptive margins in the anterior, superior, left, and right directions. Using the proposed adaptive margins, the median residual volume was 0.71% (interquartile range 0.09%-3.55%), and the median (V(daily)) receiving the prescribed dose was 99.1% (interquartile range 95.3%-99.9%). Adaptive plans demonstrated superior OAR sparing compared to conventional plans. CONCLUSIONS: The proposed patient-specific adaptive margin recipe for whole bladder irradiation resulted in margins smaller than conventional ones, optimized normal tissue sparing, and maintained adequate PTV coverage.	bladder
A Novel Approach for Bladder Cancer Treatment: Nanoparticles as a Drug Delivery System.	Bladder cancer represents one of the most prevalent malignant neoplasms of the urinary tract. In the Asian context, it represents the eighth most common cancer in males. In 2022, there were approximately 613,791 individuals diagnosed with bladder cancer worldwide. Despite the availability of efficacious treatments for the two principal forms of bladder cancer, namely non-invasive and invasive bladder cancer, the high incidence of recurrence following treatment and the suboptimal outcomes observed in patients with high-grade and advanced disease represent significant concerns in the management of bladder cancer at this juncture. Nanoparticles have gained attention for their excellent properties, including stable physical properties, a porous structure that can be loaded with a variety of substances, and so on. The in-depth research on nanoparticles has led to their emergence as a new class of nanoparticles for combination therapy, due to their advantageous properties. These include the extension of the drug release window, the enhancement of drug bioavailability, the improvement of drug targeting ability, the reduction of local and systemic toxicity, and the simultaneous delivery of multiple drugs for combination therapy. As a result, nanoparticles have become a novel agent of the drug delivery system. The advent of nanoparticles has provided a new impetus for the development of non-surgical treatments for bladder cancer, including chemotherapy, immunotherapy, gene therapy and phototherapy. The unique properties of nanoparticles have facilitated the combination of diverse non-surgical therapeutic modalities, enhancing their overall efficacy. This review examines the recent advancements in the use of nanoparticles in non-surgical bladder cancer treatments, encompassing aspects such as delivery, therapeutic efficacy, and the associated toxicity of nanoparticles, as well as the challenges encountered in clinical applications.	bladder
Proteome-wide Mendelian randomization and therapeutic targets for bladder cancer.	OBJECTIVE: To identify therapeutic protein targets for bladder cancer (BCa) using Mendelian randomization (MR) and assess potential adverse effects of these targets. METHODS: A proteome-wide MR study was conducted to determine causal relationships between plasma proteins and BCa risk. In the discovery stage, the plasma proteins (Exposure) were sourced from the R10 of Finnish database, Olink (619 samples across 2925 proteins) and SomaScan (828 samples across 7596 proteins), and Iceland database. In the replication stage, plasma proteins (Exposure) were sourced from the UK-Biobank-PPP database (54,219 participants and 2940 proteins). Summary-level data for BCa (Outcome) were obtained from the UK Biobank (UKB-SAIGE: cancer of bladder) in the discovery phase and the FinnGen consortium (FinnGen R11: cancer of bladder) in the replication phase. Colocalization and fix-effect meta-analyses were performed to validate MR findings. Finally, phenome-wide association study (Phe-WAS) was conducted to explore the side effects of druggable proteins utilizing UKB-SAIGE encompassing 783 phenotypes. RESULTS: The MR analysis identified PSCA, LY6D, and SLURP1 as proteins with a genetic association to BCa risk. SLURP1 was confirmed in the replication phase, with a meta-analysis showing an odds ratio of 1.50 (95% CI: 1.30-1.74, P < 0.001). Phe-WAS indicated potential side effects for these targets. CONCLUSION: This study provides insights into the causal relationships of plasma proteins with BCa, identifying PSCA, LY6D, and SLURP1 as potential therapeutic targets, with implications for future BCa treatment strategies.	bladder
Genetic polymorphisms, methylation, and expression levels in the GSTP1 and MGMT genes in urothelial bladder tumors.	BACKGROUND: Alteration in DNA repair and metabolism genes can affect the maintenance of DNA integrity or xenobiotics metabolism, potentially leading to DNA damage accumulation. The present study investigated the association between polymorphisms in Glutathione S-Transferase Pi 1 (GSTP1, rs1695) and O-6-Methylguanine-DNA Methyltransferase (MGMT, rs2308321) genes with urothelial bladder cancer (UBC) susceptibility and prognosis. Furthermore, the methylation patterns of the promoter region of these genes were analyzed in tumor and non-tumor bladder tissues, besides MGMT gene expression in tumor samples. METHODS AND RESULTS: Blood samples of 295 patients and 295 healthy controls were genotyped using TaqMan probe assays. The DNA of 39 bladder tumors and 4 adjacent non-tumor samples were used in the Methylation-Sensitive High-Resolution Melting (MS-HRM) assay. Neither polymorphism conferred UBC susceptibility/protection or affected tumor grade, muscle invasion, and recurrence). GSTP1 did not show methylation in the promoter region, while in the MGMT gene, all samples presented heterogeneous methylation with no significant differences between tumor and non-tumor tissues. High MGMT expression was associated with low-grade (p = 0.0153) and trends related to non-invasive tumors (p = 0.070). CONCLUSIONS: In our cohort, MGMT expression seems helpful as a biomarker of good prognosis (low-grade and absence of muscle invasion). A heterogeneous methylation pattern in the MGMT gene requires additional investigation to elucidate its potential implications.	bladder
Trop-2 and Ephrin B2 expression in urothelial carcinoma with divergent differentiation and aggressive urothelial carcinoma subtypes.	OBJECTIVES: Urothelial carcinomas (UCs) encompass a heterogeneous group of tumors. Several histopathologic features are associated with poor clinical outcomes and limited treatment options. With new rising therapeutic modalities, we aimed to determine the pattern of expression of Trop-2 and ephrin B2 in UC with aggressive subtype histology and/or divergent differentiation (SH/DD). METHODS: We performed a retrospective analysis of 113 UC samples with SH/DD at our institution from 2011 to 2021. Immunohistochemical staining for Trop-2 and ephrin B2 expression was performed on all cases. Expression was determined by the percentage of samples with a moderate or strong H-score. RESULTS: Our results show Trop-2 expression was the highest in squamous cell carcinoma and UC with squamous differentiation, adenocarcinoma and UC with glandular differentiation, and plasmacytoid subtype, while ephrin B2 expression was highest in adenocarcinoma, UC with glandular differentiation, and small cell carcinoma. CONCLUSIONS: Expression of Trop-2 and ephrin B2 may demonstrate therapeutic possibilities for patients with SH/DD, who usually have limited treatment options, particularly in small cell carcinoma, in which few targets have been identified. Clinical trials to investigate the efficacy of these novel treatments are warranted.	bladder
FDA Approval Summary: Nadofaragene Firadenovec-vncg for Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer.	On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months. The major efficacy outcome measures were complete response (CR) at any time and duration of response. Fifty subjects experienced CR 3 months after the initial treatment (CR = 51%; 95% confidence interval, 40.7; 61.3%), of whom 46% remained in response for ≥12 months. The median duration of response was 9.7 months (range: 3-52+). Common adverse reactions included instillation site discharge, fatigue, bladder spasm, micturition urgency, hematuria, chills, pyrexia, and dysuria. The approval of nadofaragene firadenovec provides a new therapy option for patients with BCG-unresponsive NMIBC with CIS who are ineligible for cystectomy.	bladder
Fluorinated chitosan mediated transepithelial delivery of sanguinarine-loaded platinum (IV) prodrug for intravesical instillation therapy of muscle-invasive bladder cancer.	Cisplatin-based neoadjuvant chemotherapy is first-line strategy to inhibit progression and metastasis of muscle-invasive bladder cancer (MIBC). However, its clinical efficacy is often limited by drug resistance and severe systemic side effects, highlighting the urgent need for innovative therapeutic approaches. Despite advancements in cisplatin-based regimens, research on intravesical cisplatin delivery systems remains scarce. In this study, we developed an amphiphilic platinum(IV) prodrug micellar platform (Pt (IV)-DI-PEG) capable of efficiently encapsulating sanguinarine (San), which was further coated with fluorinated chitosan (FCS) to construct San@Pt(IV)-DI-PEG@FCS nanoparticles (SPFNPs) for intravesical instillation even targeting MIBC. The resulting SPFNPs demonstrated several advantages: the FCS coating facilitated enhanced trans-epithelial drug delivery by regulating bladder epithelial tight junction proteins, enabling efficient intravesical administration; Second, the glutathione (GSH)-responsive reduction of the Pt(IV) prodrug promoted tumor-targeted release of San and localized accumulation of Pt(II), while simultaneously depleting intracellular GSH. Furthermore, the released San induced reactive oxygen species (ROS) production, oxidative cleavage and inhibit the activation and function of poly (ADP-ribose) polymerase, collectively impairing nucleotide-excision repair and preventing the elimination of Pt-DNA adducts, resulting in persistent DNA damage, cell cycle arrest, and apoptosis in tumor cells. The synergistic effects of San and cisplatin were validated in both orthotopic mouse models and patient-derived orthotopic xenograft, demonstrating robust anti-tumor efficacy. This study underscores the potential of intravesical cisplatin formulations as a promising strategy for MIBC treatment, offering a shift from traditional systemic chemotherapy towards localized, targeted drug delivery systems.	bladder
State of the art of adjuvant immunotherapy in urothelial cancer: New developments and upcoming changes.	In recent years, several clinical trials focused on the potential role of immune-checkpoint inhibitors (ICIs) in the adjuvant treatment of muscle-invasive urothelial cancer (UC). Heretofore, only the anti-programmed death protein 1 (anti-PD1) nivolumab received European Medical Agency (EMA) approval for cisplatin-unfit patients. In our work, we deeply analyzed the results of the three pivotal studies in view of the rapidly evolving therapeutic advanced UC's scenario. Furthermore, there are several ongoing research to investigate ICIs and other emerging immune agents in this setting; results are awaited. Additionally, current efforts have been made to assess the role of these agents in earlier disease settings, particularly in high-risk non-muscle-invasive bladder cancer (NMIBC). In our review, we analyzed the potential role of predictive and/or prognostic biomarkers that may improve patient selection and treatment efficacy. To conclude, we highlighted the upcoming changes that could redefine the standard of care for patients with early-stage UC.	bladder
Evaluation of Gemcitabine and Carboplatin Dosing in Patients With Cisplatin-Ineligible Metastatic Urothelial Carcinoma.	BACKGROUND: The National Comprehensive Cancer Network Bladder Cancer Guidelines recommend carboplatin and gemcitabine first-line treatment in patients with cisplatin-ineligible, metastatic urothelial cancer (mUC) -- a Category 1 recommendation. For these patients, the median overall survival is 9.3 months. While carboplatin is purported to offer a more tolerable side-effect profile, many patients still require dose-reductions, dose-delays, and hospitalizations. Given the inability for mUC patients to tolerate this palliative regimen, we aim to determine whether initiating therapy with a lower dose regimen is justified. METHODS: A single-institution retrospective analysis was conducted to review eligible patients treated with carboplatin plus gemcitabine from May 2014 through October 2022. Data collected via manual chart review included patient baseline characteristics, chemotherapy doses, reductions, delays, toxicities, and effectiveness. RESULTS: Forty-three patients met inclusion criteria. Nineteen patients (44%) required ≥ 1 dose reduction during therapy. Twenty-six patients (60%) started with a full-dose regimen, and 14 (54%) of those patients required a dose reduction during treatment. Seventeen patients (40%) started with a reduced-dose regimen, and 5 (29%) of those patients required a dose reduction during treatment. No patients received the anticipated 6 cycles at full dose, but 14% completed 6 cycles with dose reductions. One patient (2%) was able to tolerate >80% relative dose intensity of both carboplatin and gemcitabine. CONCLUSIONS: Cisplatin-ineligible mUC patients were unable to tolerate full-dose carboplatin and gemcitabine. As this is a palliative regimen, it would be pertinent to consider starting therapy at a reduced dose to minimize treatment interruptions, dose omissions and side effects.	bladder
A novel mouse model of upper tract urothelial carcinoma highlights the impact of dietary intervention on gut microbiota and carcinogenesis prevention despite carcinogen exposure.	Animal models of N-butyl-N-(4-hydroxy butyl) nitrosamine (BBN)-induced urothelial carcinoma (UC), particularly bladder cancer (BC), have long been established. However, the rare incidence of BBN-induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC. To address this problem, we tried to establish a novel mouse model of UTUC by treating multiple mice strains and sexes with BBN. The molecular consistency between the UTUC mouse model and human UTUC was confirmed using multi-omics analyses, including whole-exome, whole-transcriptome, and spatial transcriptome sequencing. 16S ribosomal RNA metagenome sequencing, metabolome analysis, and dietary interventions were employed to assess changes in the gut microbiome, metabolome, and carcinogenesis of UTUC. Of all treated mice, only female BALB/c mice developed UTUC over BC. Multi-omics analyses confirmed that the UTUC model reflected the molecular characteristics and heterogeneity of human UTUC with poor prognosis. Furthermore, the model exhibited increased Tnf-related inflammatory gene expression in the upper urinary tract and a low relative abundance of Parabacteroides distasonis in the gut. Dietary intervention, mainly without alanine, led to P. distasonis upregulation and successfully prevented UTUC, as well as suppressed Tnf-related inflammatory gene expression in the upper urinary tract despite the exposure to BBN. This is the first report to demonstrate a higher incidence of UTUC than BC in a non-engineered mouse model using BBN. Overall, this model could serve as a useful tool for comprehensively investigating UTUC in future studies.	bladder